Feline calicivirus (FCV) was first described in 1957 (Fastier L. B., Am. J. Vet. Res., 1957, 18:382-389). Feline calicivirus, and the feline herpesvirus, are the principal sources of viral disease of the upper respiratory tract in domestic cats and wild felids. The FCV affects a large number of animals of the felidae family, with FCV carrying rates of the order of 15 to 20% in clinically healthy domestic cats (Coutts et al., Vet. Rec., 1994, 135:555-556; Ellis T. M., Australian Vet. J., 1981, 57:115-118; Harbour et al., Vet. Rec., 1991, 128:77-80; Reubel et al., Feline Dendistry, 1992, 22:1347-1360). After an initial phase of hyperthermia, these respiratory diseases are generally followed by buccal ulcerations (palate, tongue, lips, nose), rhinitis, conjunctivitis, possibly anorexia and asthenia. The FCV can also cause pneumonia, enteritis, and articular pain (lameness syndrome).
In the last decade, FCV-associated VSD has emerged in the United States of America and the United Kingdom. Several outbreaks have been associated with a high (up to 50%) mortality rate and atypical severe clinical signs (high fever, cutaneous oedema, ulcerative dermatitis and jaundice).
The FCV is transmitted only horizontally, there is no vertical transmission from the mother to its kitten during gestation (Johnson R. P., Res. Vet. Sci., 1984, 31:114-119). FCV is transmitted by contact between infected animals and healthy animals or by the airways during sneezing (Wardley R C., Arch. Virol., 1976, 52:243-249). Feline calicivirus of the caliciviridae family is a non-enveloped virus, with a single-stranded positive RNA (Radfor et al., Proc. 1st Int. Symp., Caliciviruses ESVV, 1997, 93-99). The FCV capsid is constituted with a single major capsidal protein of 66 kDa, the p66 protein. The majority of the commercial FCV vaccines are attenuated vaccines.
A few inactivated vaccines are available. Povey and coworkers (Povey et al., Feline Practice, 1978, 8(3):35-42) describe a formalin inactivated and adjuvanted FCV preparation used in cats. U.S. Pat. Nos. 6,534,066 and 7,850,978 describe the use of new strains of FCV for the production of FCV vaccines. The inactivated vaccines usually contain an adjuvant to improve the immune response and to induce a better protection against heterologous FCV strains emerging in the cat population.
However adjuvanted vaccines induce a higher rate of local adverse reactions than non-adjuvanted ones (Gobar et al., JAVMA, 2002, 220(10), 1477-1482) and thereby increase the risk of vaccine-associated fibrosarcomas at the injection site (Baker R. J., Feline Practice, 1998, 26(5), 18-20).
Non-adjuvanted FCV vaccines are modified live vaccines usually containing the F9 strain. The residual virulence of FCV F9 has been reported by several authors in post-vaccinal calicivirosis (Dawson et al., Vet. Rec. 1993, 132:346-350). FCV modified live strains are implicated in the emergence of new antigenic variants in the field (Radford et al., Vaccine, 1997, 15(12/13), 1451-1458). The safety of modified live vaccines is therefore questionable.
FCV is a member of the Caliciviridae. It has a 7.7-kb positive-sense RNA genome with three open reading frames (ORFs), encoding the nonstructural protein, the major capsid protein (Carter et al., 1992, Arch. Virol., 122:223-235; Tohya et al., 1997, J. Gen. Virol., 78 (pt. 2), 303-305), and a minor structural protein (Sosnovtsev et al., 2005, J. Virol., 79, 4012-4024). Genetically, FCV strains belong to one diverse genogroup, with little evidence for subspecies clustering. This genetic diversity is accompanied by antigenic diversity, although there is sufficient cross-reactivity that all isolates are deemed to belong to a single serotype.
The capsid proteins from several strains of human calicivirus have been expressed in insect cells infected with recombinant baculoviruses. Virus-like particles have also been produced from the vesivirus feline calicivirus (FCV) by expressing the capsid precursor in a baculovirus expression system (DeSilver et al., 1997, Expression of the complete capsid and the hypervariable region of feline calicivirus in the baculovirus expression system. In: First International Symposium on Caliciviruses. pp. 131-143) where immunization of cats was done with a crude harvest of baculovirus infected insect sf9 cells. The non-inactivated baculovirus has an adjuvant effect (Hervas-Stubbs et al., Journal of Immunology, 2007, 178: 2361-2369; Margine et al., Plos One December 2012|Volume 7|Issue 12|e51559). The insect cells or fractions are used as adjuvants to enhance the immunogenicity of an antigen (U.S. Pat. No. 6,224,882). Di Martino et al. (2007, Vet. Microbiol., 120, 173-178) discuss the expression of FCV capsid VP1 protein in insect cells and the in vitro neutralization of FCV strains using the expressed capsid VP1 protein. However, no in vivo challenge study was done to demonstrate the efficacy of the expressed capsid VP1 protein in cats.
In light of the above, it is apparent that there is a need for vaccines with an improved safety and a good efficacy, including vaccines that are against heterologous FCV strains.
Considering the susceptibility of animals (including humans, albeit rarely) to FCV, a method of preventing FCV infection and protecting animals is essential. Accordingly, there is a need for more effective, stable and safe vaccines against FCV.